Classification of COPD into different GOLD stages is based on forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) but has shown to be of limited value. The aim of the study was to relate spirometry values to more advanced measures of lung function in COPD patients compared to healthy smokers. The lung function of 65 COPD patients and 34 healthy smokers was investigated using flow-volume spirometry, body plethysmography, single breath helium dilution with CO-diffusion, and impulse oscillometry. All lung function parameters, measured by body plethysmography, CO-diffusion, and impulse oscillometry, were increasingly affected through increasing GOLD stage but did not correlate with FEV1 within any GOLD stage. In contrast, they correlated fairly well with FVC%p, FEV1/FVC, and inspiratory capacity. Residual volume (RV) measured by body plethysmography increased through GOLD stages, while RV measured by helium dilution decreased. The difference between these RV provided valuable additional information and correlated with most other lung function parameters measured by body plethysmography and CO-diffusion. Airway resistance measured by body plethysmography and impulse oscillometry correlated within COPD stages. Different lung function parameters are of importance in COPD, and a thorough patient characterization is important to understand the disease.
Spirometry and body plethysmography are the most commonly used methods to diagnose, characterize, and assess chronic pulmonary obstructive disease (COPD). The global initiative of obstructive lung diseases (GOLD) classification of COPD [
It has long been known that spirometry measures mostly the proximal parts of the airway, while COPD is mostly a disease of the distal airways [
It is therefore important to use plausible lung function measurements for a satisfactory diagnosis and monitoring of COPD. Body plethysmography and single breath helium dilution with carbon monoxide- (CO-) diffusion are two commonly used techniques to evaluate lung volumes in order to look at hyperinflation that is not reflected by spirometry. However, the helium dilution method is known to underestimate lung volumes, while body plethysmography measures increased lung volumes in obstructive patients [
Impulse oscillometry (IOS) can detect distal airway malfunctions that are not measured with normal spirometry. COPD patients have a higher total resistance (R5), and peripheral resistance (R5–R20), and a more negative reactance at 5 Hz (X5) than healthy never-smokers [
The aim of the present study was to relate established flow-volume spirometry values to other more advanced measures of lung function using body plethysmography, single breath helium dilution with CO-diffusion and IOS in COPD patients in different stages, and healthy smokers that have not developed COPD. A secondary aim was to evaluate better characterization of lung function impairment of importance in different degrees of COPD. We hope to expand characterization of COPD patients using other parameters than from normally used flow-volume measurements to get an extended picture of the lung physiology in different COPD phenotypes.
Ninety-nine volunteers were screened with spirometry; 65 were classified as COPD patients (FEV1/FVC < 0.7) and 34 as healthy smokers (FEV1 ≥ 80%, FEV1/FVC ≥ 0.7) (Table
Patient characteristics.
Controls | GOLD1 | GOLD2 | GOLD3 | GOLD4 | |
---|---|---|---|---|---|
|
|
|
|
|
|
Female/Male, |
16/18 | 6/7 | 10/12 | 7/8 | 9/6 |
Age, years | 67 (66–70) | 68 (66–69) | 66 (61–68)** | 65 (60–69) | 66 (62–68) |
Smoker/Former smoker, |
5/29 | 7/6 | 7/15 | 1/14 | 0/15 |
Packyears | 27 (21–35) | 27 (17–45) | 31 (23–51) | 40 (30–48)** | 35 (28–40) |
Body mass index | 27 (24–28) | 26 (25–28) | 27 (24–30) | 24 (21–27) | 24 (21–27) |
No inhaled medication | 33 | 12 | 7 | 0 | 0 |
SABA use | 0 | 0 | 7 | 6 | 3 |
LAMA use | 0 | 1 | 13 | 15 | 15 |
LABA use | 1 | 1 | 11 | 11 | 14 |
ICS use | 1 | 1 | 12 | 13 | 14 |
O2 use | 0 | 0 | 0 | 2 | 5 |
CCQ-score | 4.0 (1.8–7.0) | 6.0 (2.0–10.0) | 11.0 (4.0–17.3)*** | 14.2 (19.0–21.0)***†††‡ | 25 (24–30)**† |
FEV1 (L) | 2.8 (2.3–3.4) | 2.5 (2.2–3.4) | 1.9 (1.6–2.2)***†† | 1.2 (1.0–1.4)***†††‡‡‡ | 0.7 (0.5–0.9)***†††‡‡‡### |
FEV1 (%) | 95 (90–105) | 90 ( 87–94) | 61 (55–70)***††† | 41 ( 33–49)***†††‡‡‡ | 27 (22–28)***†††‡‡‡### |
FVC (L) | 3.7 (3.0–4.3) | 4.2 (3.3–4.8) | 3.4 (2.9–4.1) | 2.9 (2.2–3.4)**††‡ | 2.1 (1.1–3.0)***†††‡‡‡# |
FVC (%) | 96 (88–103) | 106 (99–114)** | 85 (73–94)**††† | 76 (68–83)***†††‡ | 63 (35–73)***†††‡‡‡# |
FEV1/FVC | 0.77 (0.74–0.80) | 0.66 (0.63–0.70)*** | 0.58 (0.49–0.65)***†† | 0.39 (0.36–0.47)***†††‡‡‡ | 0.31 (0.30–0.46)***†††‡‡‡# |
The study was approved by the Regional Ethical Review Board in Lund (431/2008), and all study participants signed written informed consent. A physical examination was performed before the start of the study. All subjects performed IOS (Jaeger MasterScreen, Erich Jaeger GmbH, Würzburg, Germany), body plethysmography together with flow-volume spirometry (MasterScreen Body Jaeger) and single breath helium dilution with CO-diffusion test (MasterScreen Diffusion Jaeger) in given order. FEV1 and FVC were measured using established flow-volume spirometry, and FEV1/FVC was calculated. From body plethysmography (BP) inspiratory resistance (
Nonparametric unpaired data were analyzed first using the Kruskal-Wallis test for trend analyses between several groups and thereafter the Mann-Whitney test between two groups (with correction for ties). Paired data were analyzed using the Wilcoxon test. Correlations were analyzed using Spearman’s nonparametric correlation test. All statistical analyses were done using SPSS 20.0 for Windows (SPSS, Inc., Chicago, IL, USA), and a
There were no significant differences in sex or body mass index between healthy smokers and COPD patients (Table
The Kruskal-Wallis test showed an overall increasing trend among the groups for both
Body plethysmography and single breath helium dilution with CO-diffusion (SB) parameters.
Controls | GOLD1 | GOLD2 | GOLD3 | GOLD4 | |
---|---|---|---|---|---|
|
|||||
|
2.0 (1.6–2.4) | 2.0 (1.6–2.8) | 3.0 (2.1–3.2)** | 3.6 (2.8–5.3)***†††‡‡ | 35.4 (4.6–6.6)***††† ‡‡‡## |
|
3.2 (2.4–3.7) | 2.7 (2.3–4.4) | 4.8 (3.2–6.8)**†† | 13.2 (5.1–21.0)***†††‡‡ | 21.2 (14.1–33.1)***†††‡‡‡# |
IC, L | 3.2 (2.7–3.8) | 3.0 (2.7–3.7) | 2.7 (2.4–3.2) | 2.3 (1.9–3.0)***†† | 1.4 (1.0–2.6)***†††‡‡ |
IC, %p | 101 (88–108) | 97 (88–108) | 85 (73–98)† | 77 (67–91)***†† | 52 (31.66)***†††‡‡## |
|
2.5 (2.2–2.9) | 2.5 (2.3–3.0) | 2.8 (2.4–3.1) | 3.6 (3.2–4.8)***†††‡‡‡ | 4.5 (4.3–5.3)***†††‡‡‡# |
|
111 (98–120) | 115 (105–124) | 124 (100–144) | 174 (148–187)***†††‡‡‡ | 217 (193–245)***†††‡‡‡## |
|
6.4 (5.4–7.3) | 6.7 (5.7–8.1) | 6.2 (5.7–7.1) | 7.3 (6.0–7.7) | 7.0 (5.7–7.6) |
|
105 (97–111) | 108 (107–117)* | 104 (88–123) | 113 (107–126)** | 121 (100–138)**‡ |
|
3.1 (2.6–3.4) | 3.4 (3.0–4.1)* | 3.6 (3.2–4.0)** | 4.4 (3.9–5.7)***†‡‡ | 5.4 (4.6–5.8)***†††‡‡‡ |
|
94 (88–108) | 109 (102–120)** | 106 (91–142)* | 135 (123–152)***†††‡‡ | 172 (161–203)***†††‡‡‡## |
| |||||
|
|||||
|
6.2 (5.3–7.1) | 5.6 (4.5–7.7) | 5.2 (4.6–6.3)** | 3.0 (2.4–4.5)***†††‡‡‡ | 1.8 (1.1–2.5)***†††‡‡‡### |
|
75 (69–83) | 75 (53–87) | 63 (53–70)*** | 40 (32–46)***†††‡‡‡ | 22 (15–29)***†††‡‡‡### |
VA, L | 5.3 (4.7–5.3) | 5.6 (4.9–5.6) | 4.8 (4.2–5.7)† | 4.4 (4.0–5.2)*†† | 3.7 (3.1–4.5)***†††‡‡‡ |
VA, %p | 90 (83–97) | 96 (93–103)* | 84 (74–89)*††† | 78 (64–83)***††† | 67 (58–77)***†††‡‡‡ |
|
1.2 (1.1–1.3) | 1.1 (0.9–1.2)* | 1.1 (0.9–1.3)* | 0.71 (0.64–0.83)***†††‡‡‡ | 0.46 (0.35–0.56)***†††‡‡‡### |
|
89 (78–95) | 73 (61–90)* | 76 (64–93)* | 50 (45–60)***††‡‡‡ | 35 (23–41)***†††‡‡‡### |
|
1.9 (1.7–2.0) | 2.0 (1.6–2.3) | 1.7 (1.5–2.0)† | 1.5 (1.3–1.9)**† | 1.6 (1.3–1.8)* |
|
81 (72–87) | 90 (77–96) | 77 (64–89) | 67 (59–79)*† | 69 (58–95) |
|
5.5 (4.9–6.2) | 5.8 (5.1–7.1) | 5.0 (4.4–5.9)† | 4.6 (4.1–5.3)*†† | 3.9 (3.3–4.7)***†††‡‡‡ |
|
91 (85–97) | 97 (93–103)* | 85 (75–90)*††† | 79 (65–84)***††† | 68 (60–77)***†††‡‡‡ |
|
2.5 (2.1–2.7) | 3.0 (2.8–3.2)** | 2.5 (2.1–2.8)† | 2.1 (1.6–2.9)† | 2.4 (1.8–2.9)†††‡‡‡ |
|
75 (67–87) | 93 (81–104)** | 76 (66–91)†† | 71 (56–80)†† | 69 (61–102)†††‡‡‡ |
| |||||
|
|||||
RV % |
28 (19–40) | 33 (23–40) | 43 (29–62)*† | 95 (80–129)***†††‡‡‡ | 149 (119–192)***†††‡‡‡## |
TLC % |
14 (11–18) | 14 (11–18) | 18 (13–27)* | 35 (30–49)***†††‡‡‡ | 57 (39–70)***†††‡‡‡# |
An increasing trend among all the groups was seen for
DLCOSB%p (a), VA%p (b), and
An overall difference between the groups regarding diffusion capacity was detected using Kruskal-Wallis. The diffusing capacity (DLCO%p) was decreased in GOLD2–4 compared to healthy smokers. When divided by the alveolar volume (DLCO/VA) a decrease was already seen from GOLD1, due to the early increase in VA%p seen in GOLD1, and extended to GOLD4 (Figure
RV measured with body plethysmography (
RV% (a) and TLC%p (b) measured by body plethysmography and single breath helium dilution with CO-diffusion. Difference in RV% (
A similar pattern was seen for TLC, but not as pronounced as for RV. An increase in
Trends of difference between groups were detected by the Kruskal-Wallis test, and all IOS parameters showed similar patterns, with no difference between healthy smokers and GOLD1, but increasing significantly from GOLD2 (except for R20) to GOLD4 (Figure
Impulse oscillometry parameters.
Controls | GOLD1 | GOLD2 | GOLD3 | GOLD4 | |
---|---|---|---|---|---|
|
0.27 (0.23–0.32) | 0.29 (0.26–0.31) | 0.37 (0.30–0.44)***† | 0.50 (0.39–0.67)***†††‡‡ | 0.52 (0.41–0.70)***†††‡‡‡ |
|
90 (68–91) | 83 (74–97) | 105 (90–120)***† | 136 (121–195)***†††‡‡‡ | 134 (126–173)***†††‡‡‡ |
|
0.21 (0.18–0.26) | 0.22 (0.19–0.27) | 0.26 (0.20–0.28) | 0.30 (0.24–0.38)***††‡ | 0.28 (0.25–0.34)**† |
|
70 (62–89) | 79 (64–86) | 81 (73–96)* | 104 (85–130)***†††‡‡ | 89 (79–99)**† |
|
0.04 (0.03–0.08) | 0.07 (0.03–0.10) | 0.12 (0.06–0.15)***† | 0.17 (0.12–0.33)***†††‡‡ | 0.24 (0.17–0.36)***†††‡‡‡ |
|
100 (67–150) | 167 (75–192) | 250 (131–306)***† | 388 (281–554)***†††‡‡ | 425 (367–650)***†††‡‡‡ |
AX, kPa*/L | 0.18 (0.13–0.44) | 0.16 (0.11–0.57) | 0.69 (0.34–1.49)***†† | 1.64 (0.97–3.61)***†††‡‡ | 3.17 (1.46–3.54)***†††‡‡‡ |
|
10.5 (8.9–14.6) | 12.5 (9.1–15.5) | 16.4 (13.9–19.9)***†† | 20.4 (18.2–25.3)***†††‡ | 23.9 (21.3–27.7)***†††‡‡‡# |
X5, kPa*/L | −0.09 (−0.11–−0.07) | −0.08 (−0.12–−0.06) | −0.14 (−0.22–−0.10)**† | −0.25 (−0.43–−0.16)***†††‡‡ | −0.42 (−0.49–−0.23)***†††‡‡‡ |
X5 %p | 199 (104–312) | 175 (145–263) | 389 (182 –541)***† | 494 (447–795)***††† | 677 (501–859)***†††‡‡ |
R5–R20 (a) and Fres (b) measured by impulse oscillometry in controls (healthy smokers) and COPD patients with GOLD stage 1–4. *significant difference compared to healthy smokers, †significant difference compared to GOLD1, ‡significant difference compared to GOLD2, #significant difference compared to GOLD3, one symbol flagging
Due to an increasing effect in all lung function parameters with increasing GOLD stage, there was also an evident overall correlation between all lung function parameters within all subjects (data not shown). When correlating the conventionally used parameter FEV1%p within each GOLD stage, no correlation was seen with any parameters measured by body plethysmography, single breath helium dilution with CO-diffusion, or IOS. Correlations to a subset of the parameters (that differ most pronouncedly between the different GOLD stages) are shown in Table
Correlations between established flow-volume parameters and extended volume and resistance parameters.
Volume | Resistance | |||||
---|---|---|---|---|---|---|
RV%pBP-SB | TLC%pBP-SB |
|
|
|
| |
|
||||||
FEV1%p | ||||||
Controls | 0.15 |
|
|
|
|
|
GOLD1 | 0.50 |
|
|
|
|
|
GOLD2 |
|
|
|
|
|
|
GOLD3 |
|
|
|
|
|
|
GOLD4 |
|
|
|
|
|
|
FVC%p | ||||||
Controls | 0.14 | 0.34 |
|
|
|
|
GOLD1 | 0.14 | 0.15 |
|
|
|
|
GOLD2 |
|
|
|
|
|
|
GOLD3 |
|
0.01 |
|
|
|
|
GOLD4 |
|
|
|
|
|
|
FEV1/FVC | ||||||
Controls |
|
|
|
|
|
|
GOLD1 | 0.34 |
|
|
|
|
|
GOLD2 |
|
|
|
0.09 |
|
|
GOLD3 |
|
0.04 |
|
0.35 |
|
|
GOLD4 |
|
0.37 | 0.32 |
|
|
|
IC%p | ||||||
Controls | 0.30 | 0.42* | 0.07 |
|
|
|
GOLD1 | 0.29 |
|
|
|
|
|
GOLD2 |
|
|
0.06 | 0.29 |
|
|
GOLD3 | 0.11 | 0.46 |
|
0.35 |
|
|
GOLD4 |
|
0.01 |
|
|
|
|
| ||||||
|
||||||
|
||||||
Controls |
|
|
|
|
— |
|
GOLD1 |
|
0.00 | 0.44 | 0.21 | — |
|
GOLD2 | 0.08 | 0.03 |
|
|
— |
|
GOLD3 | 0.04 | 0.22 |
|
0.44 | — |
|
GOLD4 | 0.29 |
|
|
0.55 | — |
|
|
||||||
Controls |
|
|
|
|
|
— |
GOLD1 |
|
0.27 |
|
0.4 |
|
— |
GOLD2 | 0.08 | 0.02 |
|
|
|
— |
GOLD3 | 0.13 | 0.26 | 0.50 | 0.41 |
|
— |
GOLD4 |
|
0.13 |
|
0.47 |
|
— |
Data are presented as
The difference in RV%p (
An interesting finding was that resistance parameters measured by body plethysmography (
The CCQ score increased with increasing GOLD stage (Table
The main finding of this study was that established flow-volume parameters, such as FEV1, did not correlate with advanced measurements of lung volume, diffusing capacity, and resistance. This illustrates that FEV1 alone is not a good parameter when used for diagnosis and monitoring of COPD since it does not represent the whole picture of the disease. An interesting parameter was, however, the difference in RV%p measured with body plethysmography and single breath helium dilution with CO-diffusion. The
An important aim was to find a lung function parameter that may show early signs of COPD disease, since COPD is an irreversible progressive disease. When diagnosed with COPD today, the disease has already progressed to a partly irreversible limitation in airflow. It is therefore important to identify patients at an earlier stage, so that novel therapies for earlier disease progression can be developed. It is thus also important to study the initial changes in COPD leading to severe stages. Interesting findings in the present study were increases in
All lung function parameters were affected with an increasing pattern through GOLD1–4, but overall there are only minor differences between healthy smokers and GOLD1. In contrast, there are marked effects in GOLD3-4, while the patients in GOLD2 show a more variable pattern, presenting a heterogeneous group of patient with overlapping lung function results similar to both GOLD1 and GOLD3. This was most clearly seen for Fres,
Another interesting findings were the correlations between several resistance parameters measured by body plethysmography and IOS. These resistance parameters did not relate to lung volume and diffusing capacity parameters suggesting different pathological entities and thereby different COPD phenotypes. Although IOS is an easy method to use, it may not replace spirometry but could be used as a complement or in cases when spirometry cannot be performed. These findings are in accordance with previous speculations on lung diseases overall [
The use of a self-filled in quality of life questionnaire is a subjective measure and is questionable as a valuable tool in diagnosing COPD [
In conclusion, the present study shows that the use of only FEV1 in COPD diagnosis and monitoring gives an incomplete characterization of the patients. Extended lung function measurements using body plethysmography, single breath helium dilution with CO-diffusion and IOS show that there was no correlation between FEV1, and more advanced lung volume, diffusing capacity, and resistance parameters within different COPD stages. However, other flow-volume parameters, FVC, FEV1/FVC, and IC, are related to several more advanced lung function parameters. These parameters should be taken into consideration preferably when the access to more advanced equipment is limited. An interesting parameter is the difference in RV measured by body plethysmography and single breath helium dilution with CO-diffusion that gives a more pronounced measure of air trapping and hyperinflation. Different lung function parameters are of importance in different COPD stages, and a more thorough patient characterization is important for understanding the condition and giving better options for treatment in the future.
Body plethysmography
Clinical COPD Questionnaire
Chronic pulmonary obstructive disease
Global initiative of obstructive lung diseases
Forced expiratory volume in 1 s
Functional residual capacity
Forced vital capacity
Inspiratory capacity
Expiratory resistance
Inspiratory resistance
Residual volume
Total lung capacity
Diffusing capacity of the lung for carbon monoxide
Alveolar volume.
The authors report no conflict of interests.
Linnea Jarenbäck designed the study, tested the patients, analyzed and interpreted data, and co-wrote the paper. Jaro Ankerst included the patients, and revised the paper critically, Leif Bjermer designed the study, interpreted data, and revised the article critically, Ellen Tufvesson designed the study, analyzed and interpreted data and co-wrote the article.
This work was supported by Grants from the Swedish Heart and Lung foundation, Swedish Research Council, Evy and Gunnar Sandberg’s Foundation, and the Royal Physiographic Society in Lund. The authors thank the staff at the Lung and Allergy Research Unit, Skåne University Hospital, for much appreciated help and support.